Intrinsic breast cancer subtypes defined by estrogen receptor signalling—prognostic relevance of progesterone receptor loss
pmid: 23558572
Intrinsic breast cancer subtypes defined by estrogen receptor signalling—prognostic relevance of progesterone receptor loss
The majority of luminal type breast carcinomas are slowly growing tumors with an overall favorable prognosis. However, a proportion of cases (luminal B tumors) are characterized by coactivation of growth factor receptors or non-canonical ER signaling and a poorer clinical outcome. The aim of our study was to evaluate whether the expression of proteins that are part of the ER signaling network may be used to distinguish low-risk from high-risk luminal tumors. Unsupervised hierarchical clustering of a set of proteins either involved in estrogen receptor signaling or associated with resistance to endocrine therapy was performed in a series of 443 postmenopausal breast carcinomas. Using this approach, we were able to reproduce the established classification with two distinct groups of luminal (estrogen receptor positive) tumors, one group of HER2-associated tumors and a group of triple-negative tumors. However, neither proliferation nor the expression of one or more of the ER-co-factors or resistance-associated factors, but PR-expression was identified as the most important stratifier distinguishing between the two luminal groups. In fact, not only the four identified clusters were shown to be significantly associated with patient outcome, PR-expression alone or in combination with Ki-67-stains stratified ER-positive tumors into a low-risk and a high-risk group. Our data indicate that defining luminal B tumors by the presence of high-risk criteria (loss of PR-expression or increased proliferation) provides a robust and highly significant stratification of ER-positive breast carcinomas into luminal A and B.
- Ludwig-Maximilians-Universität München Germany
- Heidelberg University Germany
- German Cancer Research Center Germany
- University Hospital Heidelberg Germany
- Pathologisches Institut Germany
Neoplasms, Hormone-Dependent, Biopsy, Carcinoma, Kaplan-Meier Estimate, Middle Aged, Immunohistochemistry, Disease-Free Survival, Ki-67 Antigen, Predictive Value of Tests, Multivariate Analysis, Biomarkers, Tumor, Disease Progression, Odds Ratio, Cluster Analysis, Humans, Neoplasm Grading, Aged, Cell Proliferation, Neoplasm Staging, Proportional Hazards Models
Neoplasms, Hormone-Dependent, Biopsy, Carcinoma, Kaplan-Meier Estimate, Middle Aged, Immunohistochemistry, Disease-Free Survival, Ki-67 Antigen, Predictive Value of Tests, Multivariate Analysis, Biomarkers, Tumor, Disease Progression, Odds Ratio, Cluster Analysis, Humans, Neoplasm Grading, Aged, Cell Proliferation, Neoplasm Staging, Proportional Hazards Models
8 Research products, page 1 of 1
- 2017IsRelatedTo
- 2013IsAmongTopNSimilarDocuments
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2017IsRelatedTo
- 2019IsRelatedTo
- 2017IsRelatedTo
- 2019IsRelatedTo
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).56 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
